From natural history studies, intraplaque hemorrhage (IPH) in the carotid atherosclerotic lesion has been associated with an acceleration of plaque burden growth and an increased risk of future stroke development. While there are clear indications of the critical sequelae consequent of IPH in the carotids, effects of medical therapy on IPH and the true neurological impact of IPH remain undetermined. The overall goal of this project is to determine if aggressive medical therapy alters the natural history of carotid atherosclerotic disease in patients with IPH. The central hypothesis of this proposal is that despite statin therapy and aggressive regulation of blood pressure, carotid lesions with IPH are irrecoverably compromised compared to carotid lesions without IPH. Since IPH has been recognized at all levels of carotid stenosis, the identification of benefits, if any, from medical therapy is a critical gap in the current knowledge of carotid atherosclerotic disease. Moreover, the identification of increased neurological ischemia (silent or overt) despite aggressive medical therapy may substantially alter the management in patients with IPH across all levels of stenosis. PUBLIC HEALTH RELEVANCE: Despite ongoing research and increasing knowledge about atherosclerosis, heart disease and stroke remain the first and third leading causes of death, respectively, in the United States. This proposal seeks to investigate the mechanisms behind intraplaque hemorrhage-a component of atherosclerotic plaque- in the carotid artery by development of quantitative MRI techniques and the performance of a study to monitor the effectiveness of current medical therapies on patients with intraplaque hemorrhage. This may lead to improved diagnoses and medical therapies for these patients, as well as new techniques for the study of atherosclerosis.